Osteoporosis a major public health problem of our time, yet we are uncertain of its cause and inadequate in its treatment. We believe that further progress requires a better understanding of the factors and mechanisms regulating bone mass. We have, therefore, designed a center to support five projects that build from basic studies on the biology of bone cells, through animal models to clinical, epidemiological, and therapeutic investigations. Using a new in vitro model, Project 1 will focus on the mode of action and regulation of the osteoclast and the interaction of these cells with others present in the skeleton. Project 2 will probe the interrelationships among the calcium/vitamin D endocrine system, ovarian hormone function and bone loss using a combination of animal models and human studies. In Project 3, we will evaluate the physiological responses to phosphate administration in healthy and osteoporotic subjects and explore the efficacy of phosphate as a skeletal activator. Project 4 will combine an epidemiological approach with a prospective study to identify the factors that are important in the achievement of maximal skeletal mass after cessation of growth. Project 5 will draw together several common themes of the center to address the issue of treatment of established osteoporosis. New knowledge on the effects of phosphate on skeletal metabolism, and altered vitamin D metabolism in osteoporosis will be used to design novel treatment protocols. The rapid emergence of our center as a nationally recognized research group in metabolic bone disease, together with the demographics of the New York Metropolitan area, afford us a unique opportunity for the development of a Specialized Center of Research in Osteoporosis.